[English] 日本語
Yorodumi
- PDB-7lfs: Crystal structure of the epidermal growth factor receptor extrace... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7lfs
TitleCrystal structure of the epidermal growth factor receptor extracellular region with A265V mutation in complex with epiregulin
Components
  • Isoform 4 of Epidermal growth factor receptor
  • Proepiregulin
KeywordsSIGNALING PROTEIN / receptor / epiregulin / glioblastoma / cancer / mutation / extracellular / asymmetric / dimer / ErbB1 / EGFR
Function / homology
Function and homology information


luteinizing hormone signaling pathway / ovulation / ovarian cumulus expansion / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / ERBB2-ERBB4 signaling pathway / primary follicle stage / female meiotic nuclear division / PI3K events in ERBB4 signaling / transmembrane receptor protein tyrosine kinase activator activity ...luteinizing hormone signaling pathway / ovulation / ovarian cumulus expansion / ERBB4-ERBB4 signaling pathway / negative regulation of smooth muscle cell differentiation / ERBB2-ERBB4 signaling pathway / primary follicle stage / female meiotic nuclear division / PI3K events in ERBB4 signaling / transmembrane receptor protein tyrosine kinase activator activity / positive regulation of innate immune response / mRNA transcription / oocyte maturation / multivesicular body, internal vesicle lumen / negative regulation of cardiocyte differentiation / epidermal growth factor receptor binding / Shc-EGFR complex / positive regulation of protein kinase C signaling / Inhibition of Signaling by Overexpressed EGFR / epidermal growth factor receptor activity / EGFR interacts with phospholipase C-gamma / regulation of peptidyl-tyrosine phosphorylation / epidermal growth factor binding / response to UV-A / PLCG1 events in ERBB2 signaling / ERBB2-EGFR signaling pathway / morphogenesis of an epithelial fold / PTK6 promotes HIF1A stabilization / ERBB2 Activates PTK6 Signaling / digestive tract morphogenesis / Signaling by EGFR / intracellular vesicle / negative regulation of epidermal growth factor receptor signaling pathway / eyelid development in camera-type eye / cerebral cortex cell migration / protein insertion into membrane / ERBB2 Regulates Cell Motility / positive regulation of protein kinase activity / protein tyrosine kinase activator activity / Respiratory syncytial virus (RSV) attachment and entry / positive regulation of cell division / Signaling by ERBB4 / PI3K events in ERBB2 signaling / keratinocyte proliferation / positive regulation of phosphorylation / anatomical structure morphogenesis / positive regulation of peptidyl-serine phosphorylation / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / SHC1 events in ERBB4 signaling / hair follicle development / MAP kinase kinase kinase activity / GAB1 signalosome / positive regulation of G1/S transition of mitotic cell cycle / embryonic placenta development / salivary gland morphogenesis / Nuclear signaling by ERBB4 / keratinocyte differentiation / Signaling by ERBB2 / TFAP2 (AP-2) family regulates transcription of growth factors and their receptors / GRB2 events in EGFR signaling / SHC1 events in EGFR signaling / transmembrane receptor protein tyrosine kinase activity / EGFR Transactivation by Gastrin / positive regulation of smooth muscle cell proliferation / positive regulation of mitotic nuclear division / GRB2 events in ERBB2 signaling / ossification / SHC1 events in ERBB2 signaling / basal plasma membrane / positive regulation of DNA repair / cellular response to epidermal growth factor stimulus / positive regulation of cytokine production / animal organ morphogenesis / positive regulation of DNA replication / epithelial cell proliferation / positive regulation of epithelial cell proliferation / Signal transduction by L1 / positive regulation of protein localization to plasma membrane / NOTCH3 Activation and Transmission of Signal to the Nucleus / cellular response to amino acid stimulus / growth factor activity / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to estradiol stimulus / EGFR downregulation / wound healing / clathrin-coated endocytic vesicle membrane / Signaling by ERBB2 TMD/JMD mutants / Constitutive Signaling by EGFRvIII / cell-cell adhesion / response to peptide hormone / receptor protein-tyrosine kinase / Signaling by ERBB2 ECD mutants / negative regulation of protein catabolic process / Signaling by ERBB2 KD Mutants / positive regulation of interleukin-6 production / positive regulation of miRNA transcription / kinase binding / ruffle membrane / Downregulation of ERBB2 signaling / epidermal growth factor receptor signaling pathway
Similarity search - Function
24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Alpha-Beta Horseshoe / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain ...24 nucleotide stem-loop, u2 snrnp hairpin iv. U2 a'; Chain A / Receptor L-domain / : / Epidermal growth factor receptor transmembrane-juxtamembrane segment / Alpha-Beta Horseshoe / Tyrosine protein kinase, EGF/ERB/XmrK receptor / Growth factor receptor domain 4 / Growth factor receptor domain IV / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / EGF-like domain profile. / Growth factor receptor cysteine-rich domain superfamily / EGF-like domain signature 1. / EGF-like domain signature 2. / : / EGF-like domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Alpha Beta
Similarity search - Domain/homology
Proepiregulin / Epidermal growth factor receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 3.5 Å
AuthorsHu, C. / Leche II, C.A. / Stayrook, S.E. / Ferguson, K.M. / Lemmon, M.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Cancer Institute (NIH/NCI)R01CA198164 United States
CitationJournal: Nature / Year: 2022
Title: Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias.
Authors: Hu, C. / Leche 2nd, C.A. / Kiyatkin, A. / Yu, Z. / Stayrook, S.E. / Ferguson, K.M. / Lemmon, M.A.
History
DepositionJan 18, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 17, 2021Provider: repository / Type: Initial release
Revision 1.1Jun 1, 2022Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year
Revision 1.2Oct 18, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Revision 1.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature / Item: _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Isoform 4 of Epidermal growth factor receptor
B: Isoform 4 of Epidermal growth factor receptor
C: Isoform 4 of Epidermal growth factor receptor
D: Isoform 4 of Epidermal growth factor receptor
E: Proepiregulin
F: Proepiregulin
G: Proepiregulin
H: Proepiregulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)253,03119
Polymers248,1228
Non-polymers4,90911
Water00
1
A: Isoform 4 of Epidermal growth factor receptor
E: Proepiregulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,0004
Polymers62,0312
Non-polymers9702
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4060 Å2
ΔGint4 kcal/mol
Surface area25120 Å2
MethodPISA
2
B: Isoform 4 of Epidermal growth factor receptor
F: Proepiregulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,3845
Polymers62,0312
Non-polymers1,3533
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4530 Å2
ΔGint9 kcal/mol
Surface area25970 Å2
MethodPISA
3
C: Isoform 4 of Epidermal growth factor receptor
G: Proepiregulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,4255
Polymers62,0312
Non-polymers1,3943
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4190 Å2
ΔGint6 kcal/mol
Surface area25790 Å2
MethodPISA
4
D: Isoform 4 of Epidermal growth factor receptor
H: Proepiregulin
hetero molecules


Theoretical massNumber of molelcules
Total (without water)63,2225
Polymers62,0312
Non-polymers1,1913
Water0
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3400 Å2
ΔGint6 kcal/mol
Surface area25320 Å2
MethodPISA
Unit cell
Length a, b, c (Å)77.974, 201.331, 92.148
Angle α, β, γ (deg.)90.000, 99.040, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

-
Protein / Protein/peptide , 2 types, 8 molecules ABCDEFGH

#1: Protein
Isoform 4 of Epidermal growth factor receptor / Proto-oncogene c-ErbB-1 / Receptor tyrosine-protein kinase erbB-1


Mass: 56550.254 Da / Num. of mol.: 4 / Mutation: A265V
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGFR, ERBB, ERBB1, HER1 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P00533, receptor protein-tyrosine kinase
#2: Protein/peptide
Proepiregulin


Mass: 5480.307 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EREG / Production host: Drosophila melanogaster (fruit fly) / References: UniProt: O14944

-
Sugars , 4 types, 11 molecules

#3: Polysaccharide alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 748.682 Da / Num. of mol.: 3
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-3DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,4,3/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3/a4-b1_b4-c1_c3-d1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#4: Polysaccharide alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2- ...alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 910.823 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DManpa1-3[DManpa1-6]DManpb1-4DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/3,5,4/[a2122h-1b_1-5_2*NCC/3=O][a1122h-1b_1-5][a1122h-1a_1-5]/1-1-2-3-3/a4-b1_b4-c1_c3-d1_c6-e1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{[(4+1)][b-D-Manp]{[(3+1)][a-D-Manp]{}[(6+1)][a-D-Manp]{}}}}LINUCSPDB-CARE
#5: Polysaccharide 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose


Type: oligosaccharide / Mass: 424.401 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
DescriptorTypeProgram
DGlcpNAcb1-4DGlcpNAcb1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1b_1-5_2*NCC/3=O]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][D-1-deoxy-GlcpNAc]{[(4+1)][b-D-GlcpNAc]{}}LINUCSPDB-CARE
#6: Sugar
ChemComp-NAG / 2-acetamido-2-deoxy-beta-D-glucopyranose / N-acetyl-beta-D-glucosamine / 2-acetamido-2-deoxy-beta-D-glucose / 2-acetamido-2-deoxy-D-glucose / 2-acetamido-2-deoxy-glucose / N-ACETYL-D-GLUCOSAMINE


Type: D-saccharide, beta linking / Mass: 221.208 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C8H15NO6
IdentifierTypeProgram
DGlcpNAcbCONDENSED IUPAC CARBOHYDRATE SYMBOLGMML 1.0
N-acetyl-b-D-glucopyranosamineCOMMON NAMEGMML 1.0
b-D-GlcpNAcIUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0
GlcNAcSNFG CARBOHYDRATE SYMBOLGMML 1.0

-
Details

Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 2.75 Å3/Da / Density % sol: 55.26 %
Crystal growTemperature: 293.15 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 8 mg/ml protein, 1% w/v tryptone, 1 mM sodium azide, 50 mM HEPES (pH 7.0), 20% PEG3350

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 23-ID-B / Wavelength: 1.03318 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 14, 2020 / Details: Undulator
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03318 Å / Relative weight: 1
ReflectionResolution: 3.5→100.666 Å / Num. obs: 35094 / % possible obs: 99.2 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 3.5 % / Biso Wilson estimate: 200 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.075 / Rpim(I) all: 0.048 / Rrim(I) all: 0.089 / Rsym value: 0.075 / Net I/av σ(I): 5 / Net I/σ(I): 8.4
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique obsRpim(I) allRrim(I) allRsym valueNet I/σ(I) obs% possible all
3.5-3.693.61.2020.61788250290.7431.4161.2021.197.4
3.69-3.913.60.6771.11726248450.4210.7990.6772100
3.91-4.183.50.36421587645790.230.4310.3643.3100
4.18-4.523.30.1963.71414542490.1270.2340.1965.699.9
4.52-4.953.50.12261372639250.0770.1450.1228.599.9
4.95-5.533.70.1076.91320535830.0650.1260.1071099.9
5.53-6.393.60.0868.41119831110.0530.1010.08611.799.8
6.39-7.833.30.05712.2884826530.0370.0680.05716.299.4
7.83-11.073.20.03117.5640720240.020.0380.03125.697.8
11.07-48.0633.40.02814.6367710960.0180.0330.02837.395.2

-
Phasing

PhasingMethod: molecular replacement
Phasing MRModel details: Phaser MODE: MR_AUTO
Highest resolutionLowest resolution
Rotation8.14 Å44.38 Å
Translation8.14 Å44.38 Å

-
Processing

Software
NameVersionClassification
PHENIXdev_3915refinement
XDS20200417data reduction
SCALA3.3.22data scaling
PHASER2.8.3phasing
PDB_EXTRACT3.27data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5WB7

5wb7


Resolution: 3.5→44.38 Å / SU ML: 0.72 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 37.55 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.3148 1744 4.98 %0
Rwork0.2663 33286 --
obs0.2688 35030 99.16 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 226.37 Å2 / Biso mean: 99 Å2 / Biso min: 30 Å2
Refinement stepCycle: final / Resolution: 3.5→44.38 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms16120 0 323 0 16443
Biso mean--158.53 --
Num. residues----2184
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0 / Total num. of bins used: 12

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
3.5-3.60.44491400.40282649278995
3.6-3.720.41371490.369427922941100
3.72-3.850.38181260.347628082934100
3.85-4.010.35761550.322827542909100
4.01-4.190.37081320.303228082940100
4.19-4.410.33731570.294227762933100
4.41-4.690.3261450.262427772922100
4.69-5.050.27631310.254928082939100
5.05-5.550.35761620.27627972959100
5.55-6.350.30681510.283327652916100
6.36-80.35821400.26862806294699
8-44.380.24831560.21212746290297

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more